SREBP2m promotes proliferation and migration of hepatocarcinoma cells and inhibits apoptosis through cholesterol metabolism damage / 肿瘤
Tumor
;
(12): 318-328, 2018.
Article
in Chinese
| WPRIM
| ID: wpr-848394
ABSTRACT
Objective:
To investigate the effects of sterol regulatory element binding protein 2 (SREBP2) on the metabolism of cholesterol as well as the proliferation, apoptosis and migration of normal liver LO2 cells and hepatocellular carcinoma HepG2 cells.Methods:
By using pAd-Easy-1 adenovirus vector system, the recombinant adenovirus Ad-SREBP2m (carrying the splicing form of SREBP2) and Ad-GFP (as the control) were constructed, and then infected into LO2 and HepG2 cells, respectively. The total cholesterol level in LO2 and HepG2 cells after infection was detected by a cholesterol quantification kit. The expression levels of SREBP2m, cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and apoptosis-related proteins (including caspase 3, cleaved-caspase 3 and caspase 12) were detected by Western blotting. The effects of Ad-SREBP2m overexpression on the proliferation, cell cycle, apoptosis and migration of LO2 or HepG2 cells were detected by EdU staining method, FCM and scratch wound healing test, respectively.Results:
The recombinant adenovirus Ad-SREBP2m was successfully constructed. Compared with the Ad-GFP group, the expression levels of SREBP2m and its target protein HMGCR were up-regulated (both P 0.05); while in HepG2 cells infected with Ad-SREBP2m, the proportion of G1-phase cells decreased significantly (P < 0.001), but the proportion of S-phase cells increased significantly (P < 0.001). SREBP2m overexpression promoted the proliferation of HepG2 cells (P < 0.001), but had no effect on the proliferation of LO2 cells. The expression levels of total caspase 3, cleaved-caspase 3 and caspase 12 were significantly higher in LO2 cells infected with Ad-SREBP2m than those in Ad-GFP group (all P < 0.001), while the expression levels of total caspase 3, cleaved-caspase 3 and caspase 12 were decreased in HepG2 cells infected with Ad-SREBP2m (all P < 0.05). The apoptosis rate of LO2 cells after Ad-SREBP2m infection was increased by (11.40±0.52)% (P < 0.001), while the apoptosis rate of HepG2 cells in Ad-SREBP2m group was decreased by (4.17±0.47)% as compared with Ad-GFP group (P < 0.05). The migration distance of HepG2 cells in Ad-SREBP2m group was (1.17±0.12) mm more than that in Ad-GFP group (P < 0.05).Conclusion:
Overexpression of SREBP2m can promote the proliferation and migration and inhibit the apoptosis of hepatocellular carcinoma HepG2 cells, but it can promote apoptosis of normal liver LO2 cells.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Tumor
Year:
2018
Type:
Article
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